Prostate cancer is the second most common cancer in men, and the second leading cause of cancer death. However, when prostate cancer is diagnosed in its early stages, it can be effectively treated and cured. Combined with the digital rectal examination, the prostate specific antigen (PSA) test has been widely used to detect prostate cancer in its early stages. An elevated PSA level may be an indication of prostate cancer. However, various conditions such as enlargement or inflammation of prostate can cause elevated levels of PSA. Conversely, PSA levels may be normal despite the presence of prostate cancer. Thus, the PSA screening method for early detection of prostate cancer is not suitable due to highly prevalent false positive and negative PSA test results. Therefore, a reliable marker for early detection of prostate cancer is urgently needed. Transcriptional silencing of tumor suppressor gene expression due to hypermethylation of the gene promoters is believed to contribute to the neoplastic progression. Thus, methylated DNAs can serve as biomarkers for early detection of cancer. But, the methylation of most genes correlates positively with tumor grade and stage and thus the detection of these methylated DNAs is not necessarily suitable to identify prostate cancer at early stages, especially at stages I and II (the critical stages for effective treatment and cure). A prostate cancer gene (PCG) has recently been found to be heavily methylated in stages I and II tumor compared to the normal and later stages of tumor tissues. The methylation in the PCG allows development of PCR-based sensitive and specific tools that clearly identify the early stages of prostate cancer in tissues as well as in biological fluids such as serum and urine. The goal of the proposed studies is to establish 'proof of concept'using a large number of urine specimens. Results from these studies in combination with PSA test result will lead to the development of a non-invasive diagnostic tool not only for early detection, but also for therapeutic guidance and recurrence monitoring of prostate cancer in urine. PUBLIC HEALTH RELEVANCE Patients with prostate cancer can be effectively treated and cured, when diagnosed in early stages (i.e. the stages when the cancer is still confined to the prostate gland). The objective of this project is to develop a non-invasive, sensitive and specific method that clearly identifies the early stages of prostate cancer in urine.